The Neurobiology of Pain, Tolerance, and Addiction
WHO WE ARE Differential Mechanisms of Opioid Tolerance
One area of focus in the lab is to determine the Chronic morphine treatment increases Protein Kinase C activation signaling mechanisms which leads to the within the PAG development of tolerance to these drugs. When a person becomes tolerant to a drug, the dose must Saline Acute Morphine Chronic Morphine Dr. Erin Bobeck (PI) be increased in order to achieve the same level of pain relief, and that will lead to an increase in side effects. If we can determine what cellular changes cause tolerance, we can develop novel drugs that target these specific signaling pathways to better treat pain. Our previous studies reveled that Leela Afrose Akila Ram Max McDermott commonly used opioids, such as morphine and MS student, Biology PhD student, Biology PhD student, Neuroscience fentanyl, produce analgesia and tolerance using PKC inhibition in PAG decreases morphine tolerance different signaling mechanisms. Ongoing studies
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BigLEN-GPR171 Modulates GPR171 Agonist Decreases BigLEN-GPR171 in Opioid Tolerance, Opioid Analgesia Chronic Pain Withdrawal and Addiction Chronic pain is a huge problem that affects about one-third of the First-line chemotherapies against solid tumors are highly efficacious in reducing The BigLEN-GPR171 system shows high expression in many brain regions involved in reward, U.S. population. Despite many years of research for alternatives, the tumor burden, but have many adverse side-effects including nerve damage, such as basolateral amygdala, hippocampus, and prefrontal cortex, In order for GPR171 opioids remain the most prescribed drugs to treat many types of pain, leading to chronic pain. Non-addictive, efficacious pain relievers are an area of compounds to be used as a therapeutic for pain they must show reduced side effects compared to even though they possess many side effects including addiction. We active interest, and we propose a novel target to address this pressing opioids. We find that GPR171 agonist decreases morphine tolerance and has no effect on are exploring the novel neuropeptide-receptor system (BigLEN- issue. Mice in chronic pain experience allodynia, in which hypersensitivity morphine withdrawal or reward. This suggests that when combined with morphine we can GPR171) as a pain therapeutic. To date we find that GPR171 is to small applications of pressure elicits a pain response. We found that 5 days enhance the positive effects (pain relief) but decreases the unwanted adverse effects after long- highly expressed in the periaqueductal gray, a region crucial to the of GPR171 agonist treatment led to an improvement in their term administration. pain-relieving actions of opioids, and is found in cells that co-express hypersensitivity. While there is a decrease in GPR171 receptors in the PAG of mu opioid receptors. We found that in mice a GPR171 antagonist mice that have chronic pain, the agonist can bind to the available receptors to reduces the analgesic effects of morphine, while a GPR171 agonist produce pain relief. GPR171 agonist decreases morphine tolerance, increases those effects. This leads us to suggest that GPR171 is modulating the effects of morphine, perhaps in the periaqueductal but no change in withdrawal grey, through the actions of the mu opioid receptor. GPR171 agonist can relieve touch hypersensitivity caused by neuropathic pain GPR171 6 0 5 0 ProSAAS 1 2 0
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